QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.074849v1 312/2/694    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Darvesh, A. S. Articles by Gudelsky, G. A. Search for Related Content PubMed PubMed Citation Articles by Darvesh, A. S. Articles by Gudelsky, G. A.

NEUROPHARMACOLOGY

Evidence for the Involvement of Nitric Oxide in 3,4-Methylenedioxymethamphetamine-Induced Serotonin Depletion in the Rat Brain

College of Pharmacy, University of Cincinnati, Cincinnati, Ohio (A.S.D., G.A.G.); and School of Medicine, Boston University, Boston, Massachusetts (B.K.Y.)

Production of reactive oxygen and/or nitrogen species has been thought to contribute to the long-term depletion of brain dopamine and serotonin (5-HT) produced by amphetamine derivatives, i.e., methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). In the present study, the effects of nitric-oxide synthase (NOS) inhibitors were examined on the long-term depletion of striatal dopamine and/or 5-HT produced by the local perfusion of malonate and MDMA or the systemic administration of MDMA. The effect of MDMA on nitric oxide formation and nitrotyrosine concentration also was determined. Perfusion with MDMA and malonate resulted in a 34% reduction of 5-HT and 49% reduction of dopamine concentrations in the striatum. The systemic administration of NOS inhibitors, N-nitro-L-arginine methyl ester hydrochloride and S-methyl-L-thiocitrulline (S-MTC), and the peroxynitrite decomposition catalyst Fe(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride attenuated the MDMA- and malonate-induced depletion of striatal dopamine and 5-HT. S-MTC also attenuated the depletion of 5-HT in the striatum produced by the systemic administration of MDMA without attenuating MDMA-induced hyperthermia. Additionally, the systemic administration of MDMA significantly increased the formation of nitric oxide and the nitrotyrosine concentration in the striatum. These results support the conclusion that MDMA produces reactive nitrogen species in the rat that contribute to the neurotoxicity of this amphetamine analog.

Address correspondence to: Dr. Gary A. Gudelsky, University of Cincinnati, College of Pharmacy, 3223 Eden Ave., Cincinnati, OH 45267. E-mail: gary.gudelsky{at}uc.edu

This article has been cited by other articles:

				B. Goni-Allo, M. Ramos, I. Herv'as, B. Lasheras, and N. Aguirre Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions J Psychopharmacol, March 1, 2006; 20(2): 245 - 256. [Abstract] [PDF]